Lymplhocytes from lymph nodes obtained at mastectomy from breast cancer patients have been fused with murine and human myeloma cells to obtain human-mouse and human-human hybridoma cultures that synthesize human monoclonal antibodies. The immunologic reactivities of the human Ig's were assaved with the immunoperoxidase method using tissue sections of the primary tumor from the fusion, as well as tissue sections from other primary tumors. One human IgM monoclonal antibody, derived from a human-mouse fusion was used to discriminate between mammary carcinoma cells (from 55 of 59 patients) and normal mammary epithelial cells, stroma, or lymlphocytes of the same breast. This same antibody reacted with selected non-breast carcinomas and metastatic mammary carcinoma cells in lymph nodes and at distal sites. Several human-human hybridoma cultures have also been developed that secrete human monoclonal antibodies; these human Ig's are currently being assayed for immunoreactivity to human breast carcinomas.